Rationale: Oxidative or free radical injury may be a fundamental mechanism of human disease, including many neurological disorders. Although animal models suggest that free radical damage may be important in epilepsy, little data is available on oxidant status in patients. This study is measuring serum antioxidants, and serum and urinary markers of free radical injury in human epilepsy. Methods: Patients with intractable partial epilepsy (with and without secondary generalization), and patients with non-epileptic "pseudoconvulsions" admitted to the Epilepsy Monitoring Unit are being studied, along with age and sex matched normal volunteers. The serum antioxidants, vitamin C, vitaminE, and selenium; and a traditional serum marker of lipid peroxidation, thiobarbituric acid-reacting substances (TBARS), are measured on the morning following admission. Urinary isoprostane excretion, a novel stable marker of oxidant injury in vivo, is being measured by a highly sensitive and specific gas chromatography - mass spectrometry assay for each patient group, and also following seizures in individual patients. Each patient undergoes a full nutritional evaluation. Results: Fourteen patients with intractable partial epilepsy (8 with and 6 without secondary generalized convulsions), 3 with pseudoconvulsions, and 9 control subjects have been studied to date. Selenium levels were not significantly different between the groups, and were 103 12 ug/L (mean SEM) in patients with complex partial seizures without secondary generalization, 98 7 in those with secondary generalization, 96 17 in those with pseudoconvulsions, and 96 5 in normal controls. Vitamin C levels were 2.32 0.15, 1.25 0.19, 1.50 0.17, and 1.31 0.20 mg/dl (mean SEM) in the same four groups, respectively. Although there was no significant difference between these groups,, there was a tendency for patients with complex partial seizures without convulsions to have higher vitamin C levels. In parallel with this, no obvious difference in nutritional intake has been found between the groups. Analysis of vitamin E levels, serum TBARS, and urinary isoprostane generation is ongoing. Conclusions: This continuing study is attempting to define oxidative status in patients with intractable epilepsy using established indices of antioxidant status, and traditional and novel markers of in vivo free radical injury.